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The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.
Blood Cancer J
November 2024
Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.
View Article and Find Full Text PDFAcquired Demyelination Syndrome in Children and Adolescents: 10 Years Experience from a Tertiary Care Centre in North India.
Neurol India
September 2024
Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Background: The childhood central nervous system (CNS) acquired demyelinating syndromes (ADS) can be monophasic or recurrent, with both having considerable overlap in the first decade of life.
Objectives: The objective of the study was to describe clinical and radiological features, immunological characteristics, response to therapy and difference between monophasic and first episode of recurrent disorders of pediatric-onset CNS ADS.
Methods: Case records of all patients presenting with CNS ADS to the Department of Pediatrics between January 2009 to December 2018 were retrospectively reviewed.
Quantification of deoxythioguanosine in human DNA with LC-MS/MS, a marker for thiopurine therapy optimisation.
Anal Bioanal Chem
December 2024
Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
In the treatment of diseases such as acute childhood leukaemia (ALL) and inflammatory bowel disease (IBD), the thiopurines azathioprine, 6-mercaptopurine, and 6-thioguanine are used. Thiopurines are antimetabolites and immunomodulators used to maintain remission in patients. They are all prodrugs and must be converted into the competing antimetabolites thioguanosine triphosphate and deoxythioguanosine triphosphate for final incorporation into RNA or DNA.
View Article and Find Full Text PDFMethotrexate-induced leukoencephalopathy presenting as acute-onset limb weakness in a child: a case report.
J Med Case Rep
September 2024
Colombo North Teaching Hospital, Ragama, Sri Lanka.
Article Synopsis
- Methotrexate is a key medication for treating childhood cancers like acute lymphoblastic leukemia but can lead to severe side effects such as neurotoxicity, specifically leukoencephalopathy, which usually presents with gradual neurological symptoms.
- A case involving a 10-year-old boy showed acute neurological symptoms, including limb weakness and involuntary movements, after taking oral methotrexate, a rare occurrence compared to traditional administration routes like injection.
- MRI scans revealed brain abnormalities consistent with methotrexate-induced neurotoxicity, highlighting the need for careful monitoring of neurological effects even with oral use of the drug.
Observation and Management of Juvenile Myelomonocytic Leukemia and Noonan Syndrome-Associated Myeloproliferative Disorder: A Real-World Experience.
Cancers (Basel)
August 2024
Department of Pediatrics, Ben Towne Center for Childhood Cancer Research, Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA.
Juvenile Myelomonocytic Leukemia (JMML) is a rare and clonal hematopoietic disorder of infancy and early childhood with myeloproliferative/myelodysplastic features resulting from germline or somatic mutations in the RAS pathway. Treatment is not uniform, with management varying from observation to stem cell transplant. The aim of our retrospective review is to describe the treatment and outcomes of a cohort of patients with JMML or Noonan Syndrome-associated Myeloproliferative Disorder (NS-MPD) to provide management guidance for this rare and heterogeneous disease.
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